Clofibrate-induced neoplastic development in the rat liver is associated with decreased connexin 32 expression but not with a co-ordinated shift in expression of marker enzymes

Abstract

Altered enzyme phenotype and expression of connexin 32 (C × 32), a gap junction protein were studied during the development of rat liver tumors induced by the non-genotoxic carcinogen, clofibrate. (1) In contrast to previous findings for nitrosamine-induced lesions, preneoplastic enzyme-altered foci (EAF) and neoplastic nodules (NN) lacked any clear association with degree of altered enzyme expression because of an almost complete negativity for GST-P and GGT. (2) Immunohistochemically demonstrated C × 32 spots on the hepatocyte membranes showed a clear decrease in clofibrate-induced lesions. (3) Naturally occurring EAF demonstrating GST-P and/or GGT positivity did not show a significant decrease of C × 32 counts suggesting a reversible nature. Therefore, the Cx32 decrease appears closely linked to progression of hepatocarcinogenesis irrespective of the enzyme phenotype of neoplastic focal lesions and the carcinogens used for their induction.